Recent experiments show that anti mouse immunoglobulin (Ig) becomes strongly mitogenic for mouse B lymphocytes in vitro when coupled covalently to the surface of polyacrylamide beads. Mouse spleen cells stimulated by these anti Ig beads proliferate but do not go on to high rate Ig synthesis and secretion, as shown by a reverse hemolytic plaque assay using sheep red cells coated with anti mouse Ig. I propose to use this system to investigate the cell surface events in B lymphocyte activation and the subsequent surface events and intercellular signals which regulate proliferation versus differentiation to antibody secretion. An integral part of this investigation will be the characterization of mouse B lymphocyte subsets which may differ from one another in their susceptibility to or dependence upon various inductive and regulatory signals.